title: Maintenance immunotherapy in metastatic breast cancer.
abstract: Maintenance chemotherapy provides only a modest survival advantage in metastatic breast cancer (MBC). We have previously shown that a maintenance immunotherapy (MI) regimen based on low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) improved the lymphocyte and natural killer cell (NK) counts, and CD4+/CD8+ ratio in patients with a clinical benefit from chemotherapy. With the aim of improving progression-free survival (PFS), 100 consecutive MBC patients with a clinical benefit from chemotherapy were treated with an MI. Patients with MBC were eligible if they had no evidence of progression after 6-8 courses of epirubicin-paclitaxel induction chemotherapy. Treatment consisted of low-dose IL-2 and oral RA given until progression. The primary endpoint was progression-free survival (PFS); secondary endpoints were toxicity, overall survival (OS), and changes in immunological parameters. From 04/1997 to 04/2002, 100 patients with MBC were enrolled. After a median follow-up of 49 months, median PFS and OS were 37.1 and 57.5 months, respectively. No WHO grade 3 or 4 toxicity was observed; grade 2 cutaneous toxicity and autoimmune reactions occurred in 19 and 16% of patients, respectively. A sustained improvement in lymphocytes, NKs, and in the CD4+/CD8+ ratio was observed, with respect to baseline values. In conclusion, MI with IL-2 and RA in MBC patients who do not progress after 6-8 courses of chemotherapy is well-tolerated, improves lymphocyte, NK, CD4+/CD8+ ratio, and appears to delay disease recurrence. A randomized trial is warranted.
authors.affiliation: Ospedale Civile di Avezzano, Unità Operativa di Oncologia. frecchia1946@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Gigliola
authors.initials: G
authors.lastname: Sica
authors.forename: Giampiero
authors.initials: G
authors.lastname: Candeloro
authors.forename: Stefano
authors.initials: S
authors.lastname: Necozione
authors.forename: Roberta
authors.initials: R
authors.lastname: Bisegna
authors.forename: Massimo
authors.initials: M
authors.lastname: Bratta
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000187:drug effects; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000187:drug effects; D008875:Middle Aged; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D007376:Interleukin-2; D014212:Tretinoin